Orthopedics

Feature Article 

Ollier Disease: Pathogenesis, Diagnosis, and Management

Avinash Kumar, MS; Vijay Kumar Jain, MS; Minakshi Bharadwaj, MD; Rajendra Kumar Arya, MS

Abstract

Ollier disease (Spranger type I) is a rare bone disease that is characterized by multiple enchondromatosis with a typical asymmetrical distribution and confined to the appendicular skeleton. The pathogenesis of enchondromatosis is not clearly understood. Recently, heterozygous mutations of PTHR1, IDH1 (most common), and/or IDH2 genes have been suggested by various authors as genetic aberrations. Genomic copy number alterations and mutations controlling many vital pathways are responsible for the pathogenesis of Ollier disease. A comprehensive description of all genetic events in Ollier disease is presented in this article. Clinically, Ollier disease has a wide variety of presentations. This article describes the plethora of clinical features, both common and rare, associated with Ollier disease. Multiple enchondromas are most commonly seen in phalanges and metacarpals. Radiologically, Ollier disease presents with asymmetrical osteolytic lesions with well-defined, sclerotic margins. In this article, various radiological features of Ollier disease, including radiographs, computed tomography, and magnetic resonance imaging, are also discussed. Gross pathology, cytological, and histological features of both Ollier disease and its malignant transformation are outlined. Although treatment is conservative in most cases, different possible treatment options for difficult cases are discussed. In the literature, there is a paucity of data about the disease, including diagnosis, management, prognostication, and rehabilitation, necessitating a comprehensive review to further define all of the possible domains related to this disease. [Orthopedics. 2015; 38(6):e497–e506.]

The authors are from the Department of Orthopedics (AK, VKJ, RKA) and the Department of Pathology (MB), PGIMER, Ram Manohar Lohia Hospital, New Delhi, India.

The authors have no relevant financial relationships to disclose.

Correspondence should be addressed to: Vijay Kumar Jain, MS, Department of Orthopedics, PGIMER, Ram Manohar Lohia Hospital, New Delhi, India 110001 ( drvijayortho@gmail.com).

Received: January 12, 2014
Accepted: August 04, 2014

Abstract

Ollier disease (Spranger type I) is a rare bone disease that is characterized by multiple enchondromatosis with a typical asymmetrical distribution and confined to the appendicular skeleton. The pathogenesis of enchondromatosis is not clearly understood. Recently, heterozygous mutations of PTHR1, IDH1 (most common), and/or IDH2 genes have been suggested by various authors as genetic aberrations. Genomic copy number alterations and mutations controlling many vital pathways are responsible for the pathogenesis of Ollier disease. A comprehensive description of all genetic events in Ollier disease is presented in this article. Clinically, Ollier disease has a wide variety of presentations. This article describes the plethora of clinical features, both common and rare, associated with Ollier disease. Multiple enchondromas are most commonly seen in phalanges and metacarpals. Radiologically, Ollier disease presents with asymmetrical osteolytic lesions with well-defined, sclerotic margins. In this article, various radiological features of Ollier disease, including radiographs, computed tomography, and magnetic resonance imaging, are also discussed. Gross pathology, cytological, and histological features of both Ollier disease and its malignant transformation are outlined. Although treatment is conservative in most cases, different possible treatment options for difficult cases are discussed. In the literature, there is a paucity of data about the disease, including diagnosis, management, prognostication, and rehabilitation, necessitating a comprehensive review to further define all of the possible domains related to this disease. [Orthopedics. 2015; 38(6):e497–e506.]

The authors are from the Department of Orthopedics (AK, VKJ, RKA) and the Department of Pathology (MB), PGIMER, Ram Manohar Lohia Hospital, New Delhi, India.

The authors have no relevant financial relationships to disclose.

Correspondence should be addressed to: Vijay Kumar Jain, MS, Department of Orthopedics, PGIMER, Ram Manohar Lohia Hospital, New Delhi, India 110001 ( drvijayortho@gmail.com).

Received: January 12, 2014
Accepted: August 04, 2014

Chondromas are benign, generally asymptomatic tumors of hyaline cartilage that are most commonly located in the phalanges of the hand. They are called enchondromas when they arise from the medullary canal. Rarely, they arise on the surface of the bone and are referred to as periosteal chondromas or juxtacortical chondromas.

Enchondromas are the second most common benign cartilaginous tumor after osteochondromas.1 Enchondromatosis,2 or Ollier disease, is defined by the presence of multiple enchondromas (3 or more) and characterized by an asymmetric distribution of cartilaginous lesions that can be extremely variable in terms of their size, number, location, evolution, age of onset and diagnosis, and requirement for surgery. The association of lymphangiomas with Ollier disease and Maffucci syndrome (another enchondromatosis) has been described in the literature.3,4

Epidemiology and Classification

The estimated prevalence of Ollier disease is 1 in 100,000.5–7 The true incidence of Ollier disease may be higher because mild phenotypes without skeletal deformities are sometimes not detected. Few cases of familial occurrence have been reported (Table 1).13–15

Historical Contributions to the Evolution of Ollier Disease

Table 1:

Historical Contributions to the Evolution of Ollier Disease

Spranger et al5 created a comprehensive classification of enchondromatoses based on radiographic appearance, anatomic site, and mode of inheritance. They divided enchondromatosis into 6 subtypes: type I, Ollier disease; type II, Maffucci syndrome; type III, metachondromatosis; type IV, spondyloenchondrodysplasia; type V, enchondromatosis with irregular spinal lesions; and type VI, cheirospondyloenchondromatosis. Most subtypes are nonhereditary, whereas some are autosomal dominant or recessive. Halal and Azouz16 later added 3 subtypes to this classification system based on case reports of enchondromatosis: generalized enchondromatosis with irregular vertebral lesions, generalized enchondromatosis with mucopolysacchariduria, and enchondromatosis with concave vertebral bodies. The modified Spranger classification system is widely used to address types of enchondromatosis, and the common subtypes are listed in Table 2.17

Classification of Multiple Enchondromatosis

Table 2:

Classification of Multiple Enchondromatosis

Pathophysiology

The pathogenesis of enchondromatosis is still not clearly understood. Ollier disease is basically an abnormality of development of the limb bud, which, in post-fetal life, causes the long bones to grow in diameter but not in length. Table 3 summarizes all the proposed theories regarding the pathogenesis of Ollier disease.

Proposed Theories for the Pathogenesis of Ollier Disease

Table 3:

Proposed Theories for the Pathogenesis of Ollier Disease

In 1943, Jaffe and Lichtenstein18 proposed that enchondromatous lesions are actually the displaced cartilaginous rests of normal physeal cartilage cells. This theory is still widely accepted regarding the genesis of enchondroma. There are formations of intraosseous cartilaginous foci in enchondromas that might result from the abnormalities in signaling pathways controlling the proliferation and differentiation of chondrocytes.24

Heterozygous mutations24,25 and missense mutations24 in parathyroid-related peptide type 1 receptor (PTHR1) or dysregulation in the Indian hedgehog signaling pathway (eg, overexpression of hedgehog transcriptional regulator GLI2 or activation of a hedgehog-responsive GLI2-luciferase in a PTHR1 mutant25) may cause development of enchondromatous lesions in patients with Ollier disease.

Recently, heterozygous mutations in the isocitrate dehydrogenase (IDH) gene have been related to Ollier disease, mainly IDH1 (98%) and IDH2 (2%).26–28 These mutations exhibited a phenomenon of intraneoplastic mosaicism similar to that seen in fibrous dysplasia and osteochondroma.26

The inheritance pattern of Ollier disease is unknown but is thought to not be simply a Mendelian pattern.24,31,32 Hence, it seems that Ollier disease is a manifestation of heterogeneity of various molecular defects.

Clinical Features

The pathognomonic features of Ollier disease are as follows11:

  1. Onset in early childhood

  2. Radiological changes limited to the long ends of the bone with stripping of rarefied areas; secondary involvement of epiphysis and appearance of speckling in metaphysis and epiphysis with development of growth

  3. Histological presence of cartilage in a portion of tissue taken from the radiolucent area shown on radiographs

There is a large clinical variability in the presentation of Ollier disease with respect to size, number, location, and age of onset.7,33–35 Ollier disease usually manifests in first decade of life7,36 but has also been reported in early adolescence and adulthood.37,38 These lesions usually appear and grow before puberty but soon remodel into normal bone.6,39 Whereas enchondromas occur equally in both sexes, Ollier disease is seen twice as often in men than in women.40

Patients usually present with painless bony masses (Table 4). Although lesions generally occur bilaterally, with a unilateral predominance leading to asymmetric distribution, bilateral symmetric presentation has also been described (Figure 1).41 They have a predilection for the appendicular skeleton, but the trunk bones can also be involved in severe cases.42 Enchondromas are most commonly seen in phalanges and metacarpals and are rarely seen in the carpal bones.43 Ollier disease is also frequently seen in long bones like the femur and tibia. The trochanters of the femur are commonly involved, whereas the femoral neck is relatively spared.44 Slongo et al44 reported Ollier disease in the femoral neck leading to posterior tilting of the proximal femoral epiphysis mimicking slipped capital femoral epiphysis. Other bones that can be involved are the pelvis (especially the iliac crest), fibula, and humerus, but rarely are the ribs, sternum, and skull involved7; characteristically the vertebral and craniofacial bones are not involved.42,45 The pelvis is the most frequently involved trunk bone, which can lead to scoliosis.7

Clinical Presentations of Ollier Disease

Table 4:

Clinical Presentations of Ollier Disease

Clinical photographs of both hands (A) and feet (B) showing multiple swellings.

Figure 1:

Clinical photographs of both hands (A) and feet (B) showing multiple swellings.

The most common presenting symptom is cosmetic deformity due to the presence of multiple swellings on the extremity.46 Rarely, bone shortening is the only clinical finding. This shortening may be due to the defect in the longitudinal growth of the bones. These growth disturbances are either due to an abnormal epiphyseal plate adjacent to the enchondromas or to the tethering of the epiphyseal cartilage by an abnormally thick periosteal sleeve formed in reaction to the enchondromatous lesions.47 Asymmetrical premature physeal arrest can occur, leading to deformity around the joints. Nonuniform distribution of enchondromas, mainly involving the metaphysis, may lead to angular deformity. The concavity of the angular deformity is toward the extensive enchondromatous region.47 Widening and broadening of the metaphysis occur as the bone starts growing transversely. As a result, deformities such as genu valgus and cubitus varus, limitations in joint mobility, and leg-length discrepancy may occur.48 Pathological fractures may occur due to thinning of the cortical bone over the growing lesions.49,50 Facial asymmetry and cranial nerve palsies may also occur.48 Neural compression is less frequently seen in Ollier disease than in hereditary multiple exostosis.

Various tumors are associated with Ollier disease (Table 5). The reported incidence of malignant transformation of enchondromas in Ollier disease ranges from 5% to 50%.51–56 Chondrosarcomas are the most common malignancy arising from Ollier disease and are present in approximately 25% of patients by age 40 years.57 Malignant transformation usually occurs between ages 13 and 69 years.58 Central chondrosarcomas, located centrally in the medullary cavity, may lead to sarcomatous changes in underlying enchondromas.59 The risk of sarcomatous changes of enchondromas increases in proportion to the amount of dysplastic tissue (ie, the number and size of lesions) present in the lesions and cytogenetic aberrations.51 An interstitial deletion of the short arm of chromosome 1 [del(1) (p11p31.2)] has been described in a low-grade chondrosarcoma developing in a patient with Ollier disease.60 Such deletion has also been noticed in primary chondrosarcomas. There are larger numbers of gains and losses of genomic copy numbers and their loss of heterozygosity in chondrosarcomas associated with Ollier disease than in enchondromas. They are most commonly seen in chromosomes 3p, 5q, 6q, 9p, which results in increased genetic instability.29 These secondary chondrosarcomas are generally grade I or II.57 There may also be a correlation between expression of PTHrP, PTHR1, and Bcl2 genes and the grade of malignancy in chondrosarcoma.78–81 There is an increased chance of genetic aberrations and mutations in higher-grade chondrosarcomas than in lower-grade chondrosarcomas.30 Chondrosarcomas resulting from multiple enchondromatosis mainly affect the pelvis, shoulder girdle, distal femur, and proximal tibia.57 Chondrosarcomas of the hand resulting from enchondromatosis appear to be rare.57 Muramatsu et al57 and Goto et al61 have reported chondrosarcomas in the hand resulting from Ollier disease, although rare, mainly toward the ulnar side.

Tumors Associated With Ollier Disease

Table 5:

Tumors Associated With Ollier Disease

Pain, increasing lesion size, and thinning of the cortices are typical clinical and radiological signs of transformation to low-grade chondrosarcoma.62 Features like size greater than 5 to 6 cm, more than two-thirds’ endosteal scalloping of the cortex, cortical breach, extraosseous soft tissue mass, marked uptake on bone scan, and periosteal reaction also suggest malignant transformation.63 The usual behavior of secondary chondrosarcomas in enchondromatosis is local invasion, local recurrence, and distant metastasis, most commonly to the lungs.57 Damron et al64 reported nonmonomelic, multicentric, malignant chondrosarcomas associated with Ollier disease.

Investigations

Radiographs

On plain radiographs, enchondromas typically appear as osteolytic lesions (medullary) with well-defined, sclerotic margins; endosteal erosion; and ground-glass appearance of the matrix (Figure 2). Channel-like radiolucent areas in the metaphysis with an “organ pipe” appearance in long tubular bones are common in Ollier disease.82 The lesions have punctate calcification typical of the radiographic appearance of cartilaginous matrix. Dystrophic calcification within the matrix of small cartilage masses or fragments of lamellar bone are often described as the ring and arc, flocculent, or stippled pattern of calcification commonly appreciated in long bones.82 Calcification denotes degeneration and poor vascularity of the lesions; therefore, densely calcified lesions accumulate less tracer on bone scan.83

Anteroposterior radiographs of both hands (A), fingers (B), wrist (C), leg (D), and feet (E) showing multiple well-defined, expansile lytic lesions involving the metacarpals, metatarsals, phalanges, distal end of the radius and ulna, and lower end of the tibia/fibula. No matrix mineralization is seen.

Figure 2:

Anteroposterior radiographs of both hands (A), fingers (B), wrist (C), leg (D), and feet (E) showing multiple well-defined, expansile lytic lesions involving the metacarpals, metatarsals, phalanges, distal end of the radius and ulna, and lower end of the tibia/fibula. No matrix mineralization is seen.

The bones of the hand demonstrate a characteristic globular appearance on radiographs. The radiological appearance of enchondromas occurring in flat or irregular bone may not be diagnostic. No periosteal reaction is seen in uncomplicated enchondromas.82

Computed Tomography

Computed tomography (CT) is superior to radiography in detecting matrix mineralization, calcification pattern, lobulated lesion margins, and degree and extent of endosteal scalloping (Figure 3A). This is particularly important for lesions occurring in the areas difficult to evaluate with radiographs, like the pelvis.84 Computed tomography is also useful in evaluating the size and presence of any soft tissue component, which would favor a diagnosis of chondrosarcoma, although a soft tissue component in enchondroma may occur in association with a fracture and hematoma.6 Recently, 3-dimensional reconstructed CT has provided help in surgical planning for patients with Ollier disease.85

Coronal reconstructed computed tomography scan (A) and T2-weighted magnetic resonance image (B) of the right hand confirming the presence of multiple well-defined cystic lesions. No associated soft tissue component is seen. Lesions show hyperintense signal on the T2-weighted image.

Figure 3:

Coronal reconstructed computed tomography scan (A) and T2-weighted magnetic resonance image (B) of the right hand confirming the presence of multiple well-defined cystic lesions. No associated soft tissue component is seen. Lesions show hyperintense signal on the T2-weighted image.

Magnetic Resonance Imaging

Magnetic resonance imaging (MRI) may be requested in cases of pathological fracture when lesional characterization is necessary prior to treatment.63 On MRI, the nonmineralized component of enchondromas appears as low to intermediate signal intensity lesions on T1-weighted sequences and intermediate to high signal intensity lesions on T2-weighted sequences (Figure 3B).63,86 Small speckled foci of high signal intensity, often evident on T1-weighted MRIs, are postulated to be due to the lobular growth of enchondromas, which leaves intervening residual areas of normal yellow bone marrow.63,87 Low signal intensity septa on T2-weighted MRIs are also evident, corresponding pathologically to enchondral ossification or fibrous septations.63 Following contrast administration, enchondromas exhibit central ring and arc enhancement and septal and peripheral rims of enhancement. This pattern of enhancement is also seen in chondrosarcomas. Preliminary studies performed with dynamic MRI have suggested early enhancement of chondrosarcoma as a possible useful differentiating feature.63

Bone Scintigraphy

The most common bone scintigraphic finding is increased uptake in the long bone diaphysis or metadiaphysis. Pinhole scintigraphy is helpful in determining the metabolic profile of the tumor tissue in its different evolutional stages. Enchondromas may show high uptake on fluorodeoxyglucose–positron emission tomography (FDG-PET) and can sometimes mimic a metastatic lesion in a patient being screened for metastasis.88 Bone scan is also helpful in detecting and screening malignant transformation like chondrosarcoma because the majority (82%) of long-bone chondrosarcomas reveal intense uptake on bone scans, whereas long-bone enchondromas show mild to moderate increased radiotracer activity in only 21% of cases. In addition, a heterogeneous pattern of uptake is seen in 63% of long-bone intramedullary chondrosarcomas vs 30% of enchondromas.63 Tc-99m (V) DMSA scintigraphy can also be used and may be superior to Tc-99m MDP scintigraphy for distinguishing benign and malignant chondrogenic tumors, as well as being useful in predicting malignant transformation of chondrogenic tumors.89

Pathology

Macroscopic examination of enchondromas usually shows multiple oval-shaped or round cartilaginous nodules, limited at their periphery by woven or lamellar bone and separated from each other by intertrabecular marrow spaces in the solid cartilaginous matrix with myxoid changes appearing as fraying of the matrix.35,90 Microscopically, there are sharply demarcated lobules of mature, hypocellular hyaline cartilage with few double-nucleated cells without cytologic atypia (Figure 4); however, cellularity of the tumor may vary with increased mitosis. Inside a network of trabecular bone, islands of mature, nonvesiculated hyaline cartilage cells of various sizes and shapes are embedded in abnormally dense metachromatic staining extracellular substance. The matrix does not show any myxoid change. Calcification and ossification are common, especially at the periphery of cartilage lobules. This characteristic pattern is called bone encasement.91

Cytology of an enchondroma with Giemsa stain (original magnification ×400) (A) and Papanicolaou stain (original magnification ×200) (B) showing amorphous magenta-colored material with embedded uninucleated chondrocytes. Histopathology of an enchondroma showing lobules of mature hyaline cartilage without nuclear atypia and mitosis (hematoxylin-eosin stain, original magnification ×200 [C] and ×400 [D]).

Figure 4:

Cytology of an enchondroma with Giemsa stain (original magnification ×400) (A) and Papanicolaou stain (original magnification ×200) (B) showing amorphous magenta-colored material with embedded uninucleated chondrocytes. Histopathology of an enchondroma showing lobules of mature hyaline cartilage without nuclear atypia and mitosis (hematoxylin-eosin stain, original magnification ×200 [C] and ×400 [D]).

Cytology

Needle cytology is instrumental in making the diagnosis of Ollier disease.92 Anshu et al93 reported Papanicolaou stained smears showing the presence of numerous cartilaginous fragments with angular edges. Singly scattered round cells were also present, occasionally in tight clusters. The cells had eccentrically placed round nuclei and abundant pale cytoplasm.

Binucleation, mild atypia, hypercellularity, and large pleomorphic nuclei, which would indicate malignancy in a solitary cartilaginous tumor, are acceptable features for benign enchondromas in multiple enchondromatosis.54 It is difficult to differentiate enchondromas from grade I chondrosarcomas until, in the latter, the characteristic bone marrow permeation with trapping of host lamellar bone on all sides is seen.94–96

Differential Diagnosis

Ollier disease must be differentiated from multiple hereditary exostosis. The most important criterion to distinguish enchondromas from osteochondromas as seen in multiple hereditary exostosis is the localization of bone lesions: osteochondromas are located at the bone surface and enchondromas are located in the center of bones, thus allowing radiographic distinction.59 Radiologically, Ollier disease may mimic osteitis fibrosa cystica.97

Treatment

Treatment of Ollier disease is usually conservative, unless complications occur. The lesions can be left untreated because functional impairment is usually not severe. Surgery is performed in cases of deformity, limb-length discrepancy, pathological fracture, and malignant transformation.

The important goals of the treatment are as follows98:

  1. Achieving mechanical alignment

  2. Achieving equivalent limb length for normal walking

  3. Relieving pain from a pathological fracture

Treatment is directed toward the more extensively involved limb, deformities, and complications. Shapiro47 reported that an angular deformity greater than 25° that is not balanced by reverse deformity is an indication for surgery.

Only a few treatment options are available for Ollier disease, especially for improving appearance. An oft-used modality is intralesional curettage with or without bone grafting and/or artificial bone substitute, various osteotomies, and internal fixations. These treatments do not address the problem of limb-length discrepancy. Adas et al99 showed good results with curettage and cementing in distal femur affected with Ollier disease. Osteotomy has been used, but it must be repeated many times. Also, the presence of weak bones is a problem that makes internal fixation difficult. Other modalities of surgical treatment follow.

Ilizarov Technique

The Ilizarov technique is difficult but effective in providing mechanical stabilization in patients with Ollier disease. Distraction osteogenesis enhances the conversion of abnormal cartilage of the lesion into new lamellar bone,100 without the need for intralesional curettage or bone grafting, which was proved radiographically by Jesus-Garcia et al.101 Tellisi et al102 used a multiaxial correction frame for distraction osteogenesis in a humerus affected by Ollier disease.

More wires and olive wires are required for the stabilization because the bones are weak and many enchondromas are present.

Intramedullary Nailing

Intramedullary nailing is used in patients with limb-length discrepancies. García-Cimbrelo et al103 used an intramedullary elongation nail for femoral shortening when performing intramedullary osteotomy (internal osteotomy) followed by distraction followed by intramedullary nailing. This allows a shorter treatment time and early removal of the external fixator to prevent pin-tract infections and intramedullary infections; it also prevents complications like refracture, deformity, shortening, and nonunion arising from premature removal of the external fixator.103,104 Baumgart et al105 described good results in 12 patients using intramedullary nailing with a special motorized sliding mechanism.

Corticoplasty and Diaphysectomy

Partial resection of the cortical bone with curettage of the tumor (corticoplasty) for treating hand deformity in Ollier disease has been performed by Kim et al.85 They concluded that corticoplasty resulted in cosmetic improvement without functional deterioration.

Total/subtotal diaphysectomy and reconstruction with structural autografts or allografts are usually performed for the treatment of extensive enchondromas involving the fingers.106–108

Amputation/Limb Salvage

Although ray amputation109,110 can be performed for Ollier disease of the hand depending on the severity of involvement (eg, when destruction of cortical bone and larger lesions are present), limb salvage can be performed in a severely affected hand because, despite large bony deficits after the first resection, bony regrowth can occur without the need for bone autograft.111

Rehabilitation

Physiotherapy like ultrasound, cryotherapy, CO2 laser with stretching, active mobilization, occupational therapy, and coordination exercises improve the functional ability of patients with Ollier disease.112

Prognosis

Because widely distributed enchondromas may pose fewer problems than localized ones (eg, limb shortening, asymmetry), it is difficult to assess the prognosis of Ollier disease (Table 6). Multiple enchondromas in Ollier disease have an increased rate of recurrence after surgery, so aggressive follow-up should be performed in these cases.113

Poor Prognostic Factors of Ollier Disease

Table 6:

Poor Prognostic Factors of Ollier Disease

Annual surveillance of patients with Ollier disease, both children and adults, is recommended. Periodic surveillance of the brain and abdomen for occult lesions should also be performed in these patients.

Conclusion

Ollier disease is a rare disorder characterized by asymmetrical and bilateral painless bony lesions mainly confined to the appendicular skeleton. The disorder commonly presents with cosmetic deformity, limb-length discrepancy, and pathological fractures, and it is associated with various tumors, especially chondrosarcomas. Ollier disease must be differentiated from other causes of multiple bony swellings. Given the hypercellularity of enchondromas in Ollier disease, histological distinction between benign and malignant tumors may be difficult; therefore, in suspected malignant transformation, dynamic MRI and bone scan may help the diagnosis, in addition to commonly used investigations like radiographs and CT. The treatment of Ollier disease is usually conservative; however, in some complicated cases, reconstructive surgery after excision to amputation can be performed. The overall prognosis of Ollier disease is favorable, but annual surveillance in children and adults is recommended.

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Historical Contributions to the Evolution of Ollier Disease

YearAuthor(s)Contribution
1898Ollier8,9Coined dyschondroplasie (described as a unilateral lesion)
1923Bentzon10Interpreted as a typical reaction of the bones to an active hyperemia of the bone tissues, resulting from the anomalies of the sympathetic nervous system
1935Hunter and Wiles11First to identify the key distinguishing features such as a lack of heredity, childhood onset, and unilateral involvement in Ollier disease
1958Jaffe12Defined as the presence of either circumscribed foci or large masses of cartilage in the interior of bones
1978Spranger et al5Classified and termed Ollier disease as multiple enchondromatosis

Classification of Multiple Enchondromatosis

ConditionaClinical Features
Ollier disease (Spranger type I)Multiple enchondromas of tubular and flat bones, predominantly unilateral
Maffucci syndrome (Spranger type II)Same as Ollier disease, with hemangiomas
Metachondromatosis (Spranger type III)Multiple enchondromas and exostoses
Spondyloenchondrodysplasia (Spranger type IV)Multiple enchondromas with severe platyspondyly
Enchondromatosis with irregular spinal lesions (Spranger type V)Multiple enchondromas with dysplasia of vertebral bodies
Cheirospondyloenchondromatosis (formerly generalized enchondromatosis) (Spranger type VI)Multiple enchondromas, severe hand and foot involvement, mild platyspondyly, erosion of iliac crests
DysspondylochondromatosisMultiple appendicular enchondromas with hemivertebrae, dwarfism, limb-length discrepancy
GenochondromatosisMedial clavicular enlargement, lucent lesions of long bones

Proposed Theories for the Pathogenesis of Ollier Disease

Displaced remnants of normal physeal cartilage cells18
Hamartomatous growth of cartilage cells19–21
Failure of endochondral ossification22
Migration of dysplastic nidus from physeal proliferative zone to primary ossification zone in metaphyses23
Failure of terminal differentiation of growth plate chondrocytes24
Heterozygous mutations of PTHR1 gene25
Heterozygous mutations of IDH1 and/or IDH2 gene26–28
Loss of chromosomes (Chr 6 and Chr 3), deletions, amplifications, gains, and other genomic copy number neutral structural changes of subtle genes29,30
Familial31

Clinical Presentations of Ollier Disease

Multiple swellings
Cosmetic embarrassment
Asymmetric physeal arrest
  Madelung deformity
Angular deformity
  Genu varum
  Genu valgus
  Cubitus valgus
  Coxa vara
  Coxa valga
Pelvis involvement
  Obstructed labor
  Scoliosis
Limb-length discrepancy
Gait disturbances
Pathological fractures
  Pain
  Loss of function

Tumors Associated With Ollier Disease

Chondrosarcoma51–64
Osteosarcoma54,65
Central nervous system tumors
  Chondrosarcoma-like parasellar chondrosarcoma
  Glioma, glioblastoma multiforme66
  Astrocytoma51
  High-grade anaplastic astrocytoma65,67
  Oligoastrocytoma43
  Oligodendroglioma32
Ovarian tumors
  Juvenile granulosa cell tumor51,68–73
  Sertoli-Leydig cell tumor74
Leukemia
  Chronic myeloid leukemia75
  Acute myelogenous leukemia31
Breast adenoma74
Lung tumor
  Non–small-cell lung cancer76
Fibromatosis (deep)
  Extra-abdominal desmoid tumor77

Poor Prognostic Factors of Ollier Disease

Age of onset (early age)
Malignant transformation
Gross asymmetrical distribution
Repeated surgeries

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